Pregnant women with malaria due to infection with Plasmodium falciparum suffer more adverse consequences than P. falciparum-infected nonpregnant women. The more common and serious sequelae include anemia and severe malaria with central nervous system complications. Their infants suffer intrauterine growth retardation (IUGR), low birth weight (LBW), congenital infection and high infant mortality. Although much information has been gleaned from human trials, the conditions, and moral and ethical limitations of human studies of pregnancy preclude manipulation of the system and important data are often uninterpretable due to confounding variables. Due to its close similarity to the human in its clinical and immunological responses to Plasmodium, the nonhuman primate has been widely used as a model to study malaria. Nonhuman primates are also the only animals with a villous, hemochorial placenta like that of man and are, therefore, the animal model of choice in studies of pregnancy. We have established a model of malaria during pregnancy by intravenously inoculating 10 rhesus monkeys (Macaca mulatta) during the first trimester with Plasmodium coatneyi, a "falciparum-type parasite". All 10 monkeys became parasitemic 7-14 days post-inoculation (PI). Three aborted 7-10 days PI, coincident with high peak parasitemias (41,088-374,325 parasites per mm3), while 7 monkeys carried their infants to term. These 7 infants weighed significantly less at birth than did infants born to normal mothers (p=.0038). Placental weights in the Plasmodium-infected dams were lower than those of controls (p=.0455). Symmetrical IUGR was detected by ultrasound in 1 fetus with a birth weight of 334 grams. Another LBW infant (300 gms) had ultrasound measurments within the normal range. However, this infant's condition at birth was indicative of asymmetrical growth retardation, which is usually associated with uteroplacental insufficiency. The infant with symmetric IUGR died at 5 days of age while the other is alive but congenitally infected. The cord blood smear in the congenitally-infected infant was negative and parasitemia did not manifest itself until 80 days of age. Failure to recover from anemia during the later half of pregnancy was associated with early infant mortality in 4 infants. Histologically, placental lesions resembled those seen in human placentas infected with P. falciparum. The 6 placentas from P. coatneyi-infected dams had more significant pathologic changes than did the placentas from 5 control animals. Lesions indicative of malaria chronicity were related to IUGR and LBW. No correlation could be made between degree of placental damage and fetal mortality, birth weight, or congenital infection.